We have identified a class of HIV-1 integrase (IN) inhibitors using the DOCK program. With biochemical and enzymatic data suggesting that IN acts as a dimer or higher-order oligomer, we selected a site near the interface of two monomers in the crystal structure of the catalytic core domain (residues 55-199) of Avian Sarcoma Virus (ASV) IN. The site is located 15 angstroms from the active sites. Using the DOCK program, we searched 170,000 molecules in the Available Chemicals Database (ACD) 95.1 for small molecules that could bind to this site. From the search, 30 molecules were selected for screening, revealing one molecule with an IC50 of 4 micromolar. From this inhibitor, we used similarity searching to find 5 additional molecules that inhibit IN activity with IC50 values less than 5 micromolar.